反应详情

温度

-78 °C

A stirred solution of (E)-2-[(mixture of 3α and 3β)-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]bicyclo[3,3,0]-octan-6-one (0.22 g; prepared as described in Reference Example 33 and predominantly in the 2β-configuration) in dry diethyl ether (3 ml) at -78° C. in an atmosphere of argon was treated with a solution of lithium diisopropylamide in diethyl ether (0.5 ml; 1.38M). The solution was stirred for 10 minutes at -78° C. and then treated with 4-methoxycarbonylbutanal (112 mg) at -78° C. After stirring for 10 minutes at -78° C. the reaction mixture was treated with a solution of glacial acetic acid (200 mg) in diethyl ether (400 mg) and the resulting white suspension was allowed to warm to room temperature. The mixture was then diluted with diethyl ether (20 ml) and poured into water (10 ml). The organic phase was separated and washed with aqueous sodium bicarbonate solution (5 ml; 10% w/v) and then with saturated aqueous sodium chloride solution, dried over magnesium sulphate and concentrated in vacuo. The resulting oil (0.4 g) was dissolved in benzene (0.2 ml) at 20° C. and treated with methanesulphonyl chloride (83 mg). The stirred mixture was then treated dropwise with triethylamine (0.095 ml) and stirred for a further period of 40 minutes in an argon atmosphere. The mixture was then treated with 1,8-diazabicyclo[ 5,4,0]undec-7-ene (0.51 g) and it was stirred for a further period of 2 hours. The mixture was then treated with diethyl ether (20 ml). glacial acetic acid (2 ml) and water (20 ml). The organic phase was separated and the aqueous layer was extracted with diethyl ether (2×10 ml). The combined organic solutions were washed with saturated aqueous sodium bicarbonate solution and then dried over anhydrous sodium sulphate. Concentration in vacuo, followed by chromatography on a silica gel column, using a mixture of ethyl acetate and hexane (1:9 v/v) as eluant, gave 6-[(E)-(mixture of 3α and 3β)-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-[(E)-4-methoxycarbonylbutylidene]bicyclo[3,3,0]octan-2-one (54 g), predominantly in the 6β-configuration, otherwise known as (±)-methyl (5E,13E)-(9S), [mixture of (15R) and (15S)]-6a-oxo-6,9-methano-15-tert-butyldimethylsilyloxy-15-cyclohexyl-16,17,18,19,20-pentanorprosta-5,13-dienoate.

1. customprepared
2. stirringAfter stirring for 10 minutes at -78° C. the reaction mixture
3. temperatureto warm to room temperature
4. customThe organic phase was separated
5. washwashed with aqueous sodium bicarbonate solution (5 ml; 10% w/v)
6. dry with materialwith saturated aqueous sodium chloride solution, dried over magnesium sulphate
7. concentrationconcentrated in vacuo
8. dissolutionThe resulting oil (0.4 g) was dissolved in benzene (0.2 ml) at 20° C.
9. additiontreated with methanesulphonyl chloride (83 mg)
10. additionThe stirred mixture was then treated dropwise with triethylamine (0.095 ml)
11. stirringstirred for a further period of 40 minutes in an argon atmosphere
12. additionThe mixture was then treated with 1,8-diazabicyclo[ 5,4,0]undec-7-ene (0.51 g) and it
13. stirringwas stirred for a further period of 2 hours
14. additionThe mixture was then treated with diethyl ether (20 ml)
15. customThe organic phase was separated
16. extractionthe aqueous layer was extracted with diethyl ether (2×10 ml)
17. washThe combined organic solutions were washed with saturated aqueous sodium bicarbonate solution
18. dry with materialdried over anhydrous sodium sulphate
19. concentrationConcentration in vacuo
20. additiona mixture of ethyl acetate and hexane (1:9 v/v) as eluant